Vitamin K antagonist anticoagulation in the antiphospholipid syndrome: time in therapeutic range and clinical outcomes.

BACKGROUND: Thrombosis in the antiphospholipid syndrome is still frequently treated with vitamin K antagonists with a target international normalized ratio of 2-3. Time in therapeutic range of international normalized ratio of ≥ 70% is considered optimal. Time in therapeutic range among antiphospholipid syndrome patients is not well documented and the clinical consequences of poor international normalized ratio control are uncertain. AIMS: To determine the proportion of vitamin K antagonist -treated antiphospholipid syndrome patients achieving time in therapeutic range ≥ 70%, to define the features associated with poor control and to determine its association with thrombotic and bleeding events. METHODS: This medical records review included antiphospholipid syndrome patients treated with vitamin K antagonists, between 2012-2023. The proportion of patients achieving a time in therapeutic range≥ 70% was determined and thrombotic and bleeding events were compared between patients with time in therapeutic range ​​≥ 70% versus < 70%. RESULTS: 67 antiphospholipid syndrome patients were studied. 29.9% achieved time in therapeutic range ≥ 70%. 9.1% of patients with 3 or more comorbidities achieved time in therapeutic range values ≥ 70% compared to 40% of patients with less than 3 comorbidities. Fewer recurrent arterial and overall thrombotic events occurred with time in therapeutic range ​​≥ 70%. CONCLUSIONS: A minority of antiphospholipid syndrome patients treated with vitamin K antagonist s achieve optimal anticoagulation and are at risk for recurrent thrombotic events, particularly arterial. Presence of multiple comorbidities is associated with poor international normalized ratio control. Careful monitoring of this patient population is warranted.

Marker weighting improves single-step genomic prediction reliabilities of udder health traits in Nordic Red and Jersey dairy cattle populations.

The standard single-step genomic prediction model assumes that all SNP markers explain an equal amount of genetic variance, which, however, may not be true. This is because SNPs are located in or near different genes with different functions. Therefore, it seems logical to consider SNP marker-specific weights when predicting genomic breeding values. We hypothesized that allowing differences in the amount of genetic variance explained by each SNP marker will improve prediction reliability and response to selection. To investigate this hypothesis, we first developed multi-trait standard single-step genomic models based on the current multi-trait random regression evaluation models for udder health traits of the Nordic Red (RDC) and Jersey (JER) dairy cattle populations. The models included 4 clinical mastitis (CM) traits, 3 test-day somatic cell score (SCS) traits, and the conformation traits fore udder attachment and udder depth. In the second step, we investigated the effect of applying different SNP marker weighting scenarios in the single-step genomic prediction models, for which a single-step SNP best linear unbiased prediction model was applied. We investigated the prediction reliability of the different models by forward prediction, where the last 4 years of the data were removed to estimate breeding values for validation candidates. In addition, genetic trends of the pedigree-based estimated breeding values (PEBV) and genomic enhanced breeding values (GEBV) were examined. The data sets for RDC and JER included 6.9 and 1.2 million animals of which 5.6 and 0.9 million cows had records, respectively. The number of genotyped animals was 125,789 and 64,777 for RDC and JER, respectively. Cows had repeated SCS observations but only single observations for all other traits and breeding values for all traits were modeled by one covariance function. This required modeling 12 eigenvalue breeding value coefficients for each cow and developing SNP marker weights for the principal components rather than for the biological traits. We investigated 3 SNP marker weighting scenarios: 1) a nonlinear method similar to BayesA, 2) using the classical formula 2pqû2 that accounts for allele heterozygosity, and 3) applying a mean SNP weight calculated by 2pqû2 for every 20 adjacent SNP markers. Bias, dispersion, and prediction reliability were calculated using PEBV or GEBV from the evaluation based on the full data set on those using the reduced data set. We found that the recent favorable genetic trend in CM and SCS has been accelerated since the introduction of genomic selection. The study also shows that a significant increase in prediction reliability, i.e., 0.74 vs. 0.48 for RDC and 0.72 vs. 0.41 for JER cows for CM, can be achieved with a standard single-step genomic prediction model compared with a pedigree-based prediction model. Almost all scenarios with SNP marker weighting further improved the prediction reliability between 0.5% and 12.7%. The highest improvement was achieved by weighing the SNP markers based on the 2pqû2 formula.

Differential Effects of Ephemeral and Stable Predator Chemical Cues on Spider Antipredator Behaviour.

Semiochemicals left by predators in their foraging area can be utilised by prey to avoid predation. The range of predators' chemical cues with contrasting degradation rates might provide information of different quality, potentially allowing prey to differentiate between the immediate and the longer-term presence of predators in a location. So far, knowledge about the roles of volatile versus stable chemical cues in informing predation risk is limited. We here seek to disentangle the role of ephemeral trail pheromones compared to persistent cuticular hydrocarbons of ants (predators) on the antipredator behaviour of juvenile spiders (prey), with the expectation that volatile semiochemicals induce avoidance behaviour in spiders at a higher rate compared to stable cues. We allowed the spiders to choose between sites with and without ant cues separately for volatile trail pheromones and stable hydrocarbons. Unexpectedly, spiders avoided the presence of persistent cuticular hydrocarbons more clearly than the highly volatile trail pheromone. This underscores the widespread impact of these stable cues on the avoidance behaviour of potential intraguild prey. The response to trail pheromones was unclear, possibly because spiders always encounter these cues simultaneously with visual and vibratory cues from ants; hence, trail pheromones may not contain any additional information, hindering the evolution of the ability to detect them.

Safety and efficacy of pulsed-field ablation for atrial fibrillation in the elderly: A EU-PORIA sub-analysis.

BACKGROUND: The role of catheter ablation in elderly patients with atrial fibrillation (AF) is unclear. Pulsed field ablation (PFA) demonstrates a favorable clinical profile, however, data on elderly patients are lacking. AIMS: We aimed to assess the safety and efficacy of PFA in the elderly, using data from the EU-PORIA registry. METHODS: Periprocedural complications and long-term safety and efficacy outcomes of AF ablation using the pentaspline PFA catheter (Farapulse™) were compared between patients older than 80 years old and their younger counterparts, across seven European centers. RESULTS: Among the 1233 patients in the registry, 88 (7.1 %) were older than 80 years. Elderly patients were more often females (51.1 % vs 37.8 %, p = 0.01) with a lower median BMI (26.0, IQR:23.5-29.2 vs 26.9, IQR:24.4-30.4 kg/m2, p = 0.02), a higher median CHA2DS2-VASc score (4, IQR:3-5 vs 2, IQR:1-3, p < 0.001) and a higher incidence of hypertension (73.9 % vs 52.7 %, p < 0.001). In both groups, most patients had paroxysmal AF (58.0 % vs 60.3 %, p = 0.65). Ablation in the elderly was more frequently performed with minimally interrupted anticoagulation (87.5 % vs 59.7 %, p < 0.001). Despite comparable rates of overall complications (5.7 % vs 3.5 %, p = 0.29), elderly patients had a higher incidence of stroke (2.3 % vs 0.3 %, p = 0.04). At 12 months, major adverse clinical events (4.5 % vs. 2.1 %, p = 0.12) and arrhythmia-free survival (70 % vs 74 %, p = 0.69) were comparable in both groups. None of the recurrence-free elderly patients were on antiarrhythmic drugs at the end of follow-up. CONCLUSION: In this real-world cohort, the efficacy of PFA for AF was similar in elderly and younger patients. Despite comparable complication rates, a higher incidence of stroke was observed in the elderly.

Tracking Real-World Physical Activity in Chronic Obstructive Pulmonary Disease Over One Year: Results from a Monocentric, Prospective, Observational Cohort Study.

Introduction: Lung function constraints and comorbidities such as coronary heart disease, sarcopenia, and mood disorders make chronic obstructive pulmonary disease (COPD) patients avoid physical activity (PA). However, PA represents an important pillar of COPD management and is explicitly recommended by professional associations to enhance physical functioning and positively modulate disease progression. Methods: In this monocentric, prospective, observational feasibility study, it was our primary objective to investigate the association between PA and the evolution of the COPD assessment test (CAT) and the occurrence of acute exacerbations of COPD (AECOPD), respectively. To this end, we equipped 42 COPD patients with an activity tracking wearable and telemonitored their daily PA levels over one year using a dedicated web-based interface. Patients additionally provided weekly CAT scores using the same telehealth platform and came in for 3 study visits to assess functional parameters and biochemical markers related to nutrition and inflammation. Results: A principal study finding was that PA was inversely associated with CAT score (drop of 0.21 points associated with an increase of 1000 daily steps, p = 0.004), and that the 50% of patients with higher PA levels showed less CAT score progression over time (0.42 points per year) than the 50% of patients with lower PA levels (3.26 points per year) (p < 0.001). In addition, higher PA levels were significantly associated with a lower likelihood of experiencing a moderate-to-severe AECOPD (31% risk reduction associated with an increase of 1000 daily steps, p = 0.0097). Discussion: Our study demonstrates the relevance of PA for key COPD outcome metrics in a real-world setting and underpins the importance of PA for COPD self-management in everyday life. Our study paves the way for future intervention trials to prospectively identify medically relevant PA thresholds and establish training recommendations for different patient subgroups.

Deterministic photon source of genuine three-qubit entanglement.

Deterministic photon sources allow long-term advancements in quantum optics. A single quantum emitter embedded in a photonic resonator or waveguide may be triggered to emit one photon at a time into a desired optical mode. By coherently controlling a single spin in the emitter, multi-photon entanglement can be realized. We demonstrate a deterministic source of three-qubit entanglement based on a single electron spin trapped in a quantum dot embedded in a planar nanophotonic waveguide. We implement nuclear spin narrowing to increase the spin dephasing time to T 2 * ≃ 33 ns, which enables high-fidelity coherent optical spin rotations, and realize a spin-echo pulse sequence for sequential generation of spin-photon and spin-photon-photon entanglement. The emitted photons are highly indistinguishable, which is a key requirement for scalability and enables subsequent photon fusions to realize larger entangled states. This work presents a scalable deterministic source of multi-photon entanglement with a clear pathway for further improvements, offering promising applications in photonic quantum computing or quantum networks.

YAP/TAZ signaling in allantois-derived cells is required for placental vascularization.

Normal placental development and angiogenesis are crucial for fetal growth and maternal health during pregnancy. However, molecular regulation of placental angiogenesis has been difficult to study due to a lack of specific genetic tools that isolate the placenta from the embryo and yolk sac. To address this gap in knowledge we recently developed Hoxa13 Cre mice in which Cre is expressed in allantois-derived cells, including placental endothelial and stromal cells. Mice lacking the transcriptional regulators Yes-associated protein (YAP) and PDZ-binding motif (TAZ) in allantois-derived cells exhibit embryonic lethality at midgestation with compromised placental vasculature. snRNA-seq analysis revealed transcriptional changes in placental stromal cells and endothelial cells. YAP/TAZ mutants exhibited significantly reduced placental stromal cells prior to the endothelial architectural change, highlighting the role of these cells in placental vascular growth. These results reveal a central role for YAP/TAZ signaling during placental vascular growth and implicate Hoxa13 -derived placental stromal cells as a critical component of placental vascularization.

Persistence of Structural Lubricity on Contaminated Graphite: Rejuvenation, Aging, and Friction Switches.

Using atomic force microscopy experiments and molecular dynamics simulations of gold nanoislands on graphite, we investigate why ultralow friction commonly associated with structural lubricity can be observed even under ambient conditions. Measurements conducted within a few days after sample synthesis reveal previously undiscovered phenomena in structurally lubric systems: rejuvenation, a drop in kinetic friction of an order of magnitude shortly after the onset of sliding; aging, a significant increase in kinetic friction forces after a rest period of 30 min or more; and switches, spontaneous jumps between distinct friction branches. These three effects are drastically suppressed a few weeks later. Imaging of a contamination layer and simulations provide a consistent picture of how single- and double-layer contamination underneath the gold nanoislands as well as contamination surrounding the nanoislands affect structural lubricity without leading to its breakdown.

Early Outcomes of the Surgical Treatment of Non-traumatic Massive Pericardial Effusion in the University of the Philippines - Philippine General Hospital COVID-19 Referral Center.

Objective: To describe the treatment outcomes of patients who underwent tube pericardiostomy for all etiologies of non-traumatic massive pericardial effusion or tamponade during the COVID-19 pandemic and determine the association between patient profile and treatment outcomes. Methods: Data were obtained from patients with massive pericardial effusion or cardiac tamponade who underwent surgical drainage from January 1, 2020, to September 1, 2022, in the University of the Philippines - Philippine General Hospital (UP-PGH). These patients' demographic and clinical profiles, and treatment outcomes were evaluated using frequencies and percentages. Chi-squared and Fisher's tests determined the differences between COVID (+) and (-) groups. Odds Ratio was used to assess the risk of complications and mortality. Results: The study population comprised 90 patients with a mean age of 45 years. 54.4% were females. Fifteen (16.67%) were COVID-19 (+) and 75 (83.33%) were COVID-19 (-). Most of the patients were of O+ blood type (34.4%), with no smoking history (67.8%) and no COVID-19 vaccination (76.7%). Common comorbidities were cancer (70%), tuberculosis infection (32.2%), and hypertension (25.6%). No significant difference was found between the two study groups. The presentation was subacute (one week to three months) (62.2%), with the most common symptoms of dyspnea (81.1%), orthopnea (61.1%), and cough (52.2%). Tachycardia (80%) and tachypnea (57.8%) were the most common presenting signs. Hypotension was found more frequently among COVID-19 (+) patients (46.7% vs. 12.0%, p = 0,003, 95% CI). Most patients had abnormal WBC, coagulopathy, elevated inflammatory markers, and cardiac biomarkers. Sinus tachycardia, regular sinus rhythm, ST-T wave changes, and low voltage QRS were common ECG findings. The most common chest X-ray results were pleural effusion (80%), pneumonia (71.1%), and enlarged cardiac border (42.2%). Majority of echocardiographic findings were large effusion (>2 cm) (97.8%), RV collapse (40%), and RA collapse (23.3%). An average of 628 ml of pericardial effusion was drained, predominantly serous and exudative. One specimen yielded a positive AFB culture. 6.7% showed carcinoma cells on fluid cytology. The pericardium was normal in 78.9%. 10.0% of the pericardial biopsy specimen had carcinoma, with metastatic cancer being the most common etiology. The most common cancers were lymphoma (22.7%), breast (25.8%), and lung (16.7%). Hospital length of stay was 18 days in COVID-19 (+) patients and 12 days in COVID (-). The complication and in-hospital mortality rate in the COVID-19 (+) compared to the (-) group (86.7% vs. 73.3% and 46.7% vs. 41.3%, respectively) were not statistically significant. The most common complications were respiratory failure (60%), shock (53.3%), and nosocomial pneumonia (40%). There was no association between clinical factors and the risk for complications. Any complication increased the risk for mortality (OR 15.0, 95% CI 3.2-19.7, p=0.002). The presence of hypertension (OR 0.08, 95% CI 0.02 to 0.4, p=0.001) and subacute duration (OR 0.3, 95% CI 0.09 -0.9, p=0.045) decreased the mortality risk. Conclusions: Profiles were similar in both groups. There was no association between patient profile and complications. Having COVID-19 did not affect patient outcome. The presence of any complication increases the risk of mortality. In-hospital mortality was high at 42.2%.

Disparities in the access to atrial fibrillation ablation in Denmark: who gets ablated, who neglected?

AIMS: Atrial fibrillation (AF) is a common arrhythmia associated with reduced quality of life that can lead to serious complications such as stroke and heart failure. Ablation is a safe and effective treatment for AF but is not offered equally to all patients. The aim of this study is to identify demographic groups more or less likely to undergo AF ablation. METHODS AND RESULTS: All patients with newly diagnosed AF between 2010 and 2018 were identified in the Danish nationwide registries. The association between gender, age, level of education and attachment to the job market, and the likelihood of receiving AF ablation was investigated using multivariable Cox proportional hazard analysis. Cumulative incidence was calculated using the Aalen-Johansen estimator. A total of 176 248 patients were included. Men were more likely to receive ablation than women (7% vs. 3%). Patients aged 25-44 and 45-64 were most likely to receive ablation, while only 0.7% of patients aged 80 or above received ablation. The rate of ablation significantly decreased with decreasing level of education. Full-time employed patients were most likely to receive ablation, followed by self-employed, unemployed, on sick leave, undergoing education, and early retired patients. Retired patients were the least likely to receive ablation (3%). CONCLUSION: This study found that women, older patients, patients with lower levels of education, and patients on social benefits are less likely to receive AF ablation. These findings suggest that there are significant social and economic disparities in AF ablation treatment in Denmark.

Evaluation of guided reporting: quality and reading time of automatically generated radiology report in breast magnetic resonance imaging using a dedicated software solution.

PURPOSE: Unstructured, free-text dictation (FT), the current standard in breast magnetic resonance imaging (MRI) reporting, is considered time-consuming and prone to error. The purpose of this study is to assess the usability and performance of a novel, software-based guided reporting (GR) strategy in breast MRI. METHODS: Eighty examinations previously evaluated for a clinical indication (e.g., mass and focus/non-mass enhancement) with FT were reevaluated by three specialized radiologists using GR. Each radiologist had a different number of cases (R1, n = 24; R2, n = 20; R3, n = 36). Usability was assessed by subjective feedback, and quality was assessed by comparing the completeness of automatically generated GR reports with that of their FT counterparts. Errors in GR were categorized and analyzed for debugging with a final software version. Combined reading and reporting times and learning curves were analyzed. RESULTS: Usability was rated high by all readers. No non-sense, omission/commission, or translational errors were detected with the GR method. Spelling and grammar errors were observed in 3/80 patient reports (3.8%) with GR (exclusively in the discussion section) and in 36/80 patient reports (45%) with FT. Between FT and GR, 41 patient reports revealed no content differences, 33 revealed minor differences, and 6 revealed major differences that resulted in changes in treatment. The errors in all patient reports with major content differences were categorized as content omission errors caused by improper software operation (n = 2) or by missing content in software v. 0.8 displayable with v. 1.7 (n = 4). The mean combined reading and reporting time was 576 s (standard deviation: 327 s; min: 155 s; max: 1,517 s). The mean times for each reader were 485, 557, and 754 s, and the respective learning curves evaluated by regression models revealed statistically significant slopes (P = 0.002; P = 0.0002; P < 0.0001). Overall times were shorter compared with external references that used FT. The mean combined reading and reporting time of MRI examinations using FT was 1,043 s and decreased by 44.8% with GR. CONCLUSION: GR allows for complete reporting with minimized error rates and reduced combined reading and reporting times. The streamlining of the process (evidenced by lower reading times) for the readers in this study proves that GR can be learned quickly. Reducing reporting errors leads to fewer therapeutic faults and lawsuits against radiologists. It is known that delays in radiology reporting hinder early treatment and lead to poorer patient outcomes. CLINICAL SIGNIFICANCE: While the number of scans and images per examination is continuously rising, staff shortages create a bottleneck in radiology departments. The IT-based GR method can be a major boon, improving radiologist efficiency, report quality, and the quality of simultaneously generated data.

General anaesthesia compared to conscious sedation for first-time atrial fibrillation catheter ablation-a Danish nationwide cohort study.

AIMS: Catheter ablation (CA) is a well-established treatment option for atrial fibrillation (AF), where sedation and analgesia are pivotal for patient comfort and lesion formation. The impact of anaesthesia type on AF recurrence rates remains uncertain. This study aimed to examine AF recurrence rates depending on conscious sedation (CS) vs. general anaesthesia (GA) during CA. METHODS AND RESULTS: Utilizing nationwide data from the Danish healthcare registries, we conducted this cohort study involving adults (≥18 years) undergoing first-time CA for AF between 2010 and 2018. Patients were categorized by anaesthesia type (CS or GA), with the primary endpoint being AF recurrence, defined by a composite endpoint of either antiarrhythmic drug (AAD) prescriptions, AF-related hospital admissions, electrical cardioversions, or AF re-ablation. The impact of anaesthesia type was evaluated using multivariable Cox proportional hazards analysis. The study cohort comprised 7957 (6421 CS and 1536 GA) patients. Persistent AF, hypertension, and heart failure, as well as use of AAD, were more prevalent in the GA group. Cumulative incidences of recurrent AF were higher in the CS group at 1 (46% vs. 37%) and at 5 (68% vs. 63%) years. Multivariate analysis revealed CS as significantly associated with increased risk of AF recurrence at 5-year follow-up [hazard ratio 1.26 (95% confidence interval 1.15-1.38)], consistent across paroxysmal and persistent AF subtypes. CONCLUSION: This nationwide cohort study suggests a higher risk of AF recurrence with CS during CA compared to GA. These results advocate for considering GA as the preferred anaesthesia type for improved CA outcomes.

A Multiscale Inelastic Internal State Variable Corrosion Model.

We present a corrosion internal state variable (ISV) damage model based upon the integrated computational materials engineering (ICME) hierarchical multiscale paradigm. Structure-property experiments for magnesium alloys were used where the only inputs were the volume fractions of each element of the periodic table. This macroscale ISV corrosion model finds its basis in Horstemeyer's mechanical damage model, which includes three separate ISVs for damage nucleation, growth, and coalescence, as well as Walton's inclusion of corrosion, which introduces five new ISVs for pit nucleation, growth, and coalescence, along with general corrosion and intergranular corrosion. While Walton's corrosion ISVs are phenomenological in nature, herein we develop a multiscale physical basis for the corrosion ISVs. The parameters for the macroscale corrosion ISVs were garnered from the mesoscale Butler-Volmer equations. Pure magnesium with differing amounts of aluminum were used in corrosion tests to exemplify the different pitting, general corrosion, and intergranular corrosion rates, and the macroscale ISV model was calibrated with said data, in which the only inputs to the model are the volume percentages of the elements magnesium and aluminum. Although magnesium alloys were used to motivate and calibrate the model, the model is abstract enough to possibly capture other material systems as well.

Characterisation of European Field Goat Prion Isolates in Ovine PrP Overexpressing Transgenic Mice (Tgshp IX) Reveals Distinct Prion Strains.

After the detection of bovine spongiform encephalopathy (BSE), and a zoonotic transmissible spongiform encephalopathy (TSE) caused by the pathological prion protein (PrPSc) in two goats, the investigation of goat prions became of greater interest. Therefore, a broad collection of European goat TSE isolates, including atypical scrapie, CH1641 and goat BSE as reference prion strains were biochemically characterised and subsequently inoculated into seven rodent models for further analysis (already published results of this comprehensive study are reviewed here for comparative reasons). We report here the histopathological and immunohistochemical data of this goat TSE panel, obtained after the first passage in Tgshp IX (tg-shARQ) mice, which overexpress the ovine prion protein. In addition to the clear-cut discrimination of all reference prion strains from the classical scrapie (CS) isolates, we were further able to determine three categories of CS strains. The investigation further indicates the occurrence of sub-strains that slightly resemble distant TSE strains, such as BSE or CH1641, reinforcing the theory that CS is not a single strain but a mixture of sub-strains, existing at varying extents in one isolate. This study further proved that Tgshp IX is a potent and reliable tool for the in-depth characterisation of prion strains.

Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals.

BACKGROUND: Post-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R-SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R-SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19. METHODS: Baseline serum R-SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R-SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS. RESULTS: Baseline albumin-adjusted serum R-SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R-SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = -9.48, p = 0.023). CONCLUSION: Non-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R-SH as a monitoring biomarker and a potential therapeutic target in the development of PCS.

Prognostic importance of ischemic heart disease for patients with atrial fibrillation undergoing catheter ablation.

BACKGROUND: Ischemic heart disease (IHD) has been linked to an increased risk of atrial fibrillation (AF). However, data are sparse regarding the role of IHD in AF recurrence after catheter ablation. OBJECTIVE: We sought to investigate whether preexisting or new-onset IHD is associated with a greater risk of AF recurrence after ablation. METHODS: With use of Danish nationwide registries, all patients undergoing first-time AF ablation in Denmark from 2010 to 2020 were identified. The primary outcome was AF recurrence defined by AF-related hospital admission or antiarrhythmic drug use within 1 year after ablation excluding a 3-month blanking period. IHD was defined as an International Classification of Diseases, Tenth Revision diagnosis of IHD or prior coronary revascularization. RESULTS: Of 12,162 patients undergoing first-time ablation for AF (mean age, 62 years; 30% female), 20% had preexisting IHD. Preexisting IHD was associated with an increased risk of AF recurrence in univariable log-binomial logistic regression (relative risk, 1.09; 95% CI, 1.04-1.14; P < .001). However, after multivariable adjustment including procedural year, preexisting IHD was no longer associated with an increased risk of AF recurrence (relative risk, 1.02; 95% CI, 0.97-1.06; P = .42). In a nested case-control study of those without preexisting IHD before ablation (n = 9778), newly diagnosed IHD after ablation was associated with an increased risk of AF recurrence in multivariable analysis (hazard ratio, 3.03; 95% CI, 1.84-4.99; P < .001). CONCLUSION: The presence of IHD does not appear to reduce the effectiveness of AF ablation procedures. However, the emergence of IHD after AF ablation may serve as a trigger for AF that is insufficiently suppressed by prior ablation.

Prion protein gene (PRNP) variation in German and Danish cervids.

The structure of cellular prion proteins encoded by the prion protein gene (PRNP) impacts susceptibility to transmissible spongiform encephalopathies, including chronic wasting disease (CWD) in deer. The recent emergence of CWD in Northern European reindeer (Rangifer tarandus), moose (Alces alces alces) and red deer (Cervus elaphus), in parallel with the outbreak in North America, gives reason to investigate PRNP variation in European deer, to implement risk assessments and adjust CWD management for deer populations under threat. We here report PRNP-sequence data from 911 samples of German red, roe (Capreolus capreolus), sika (Cervus nippon) and fallow deer (Dama dama) as well as additional data from 26 Danish red deer close to the German border and four zoo species not native to Germany. No PRNP sequence variation was observed in roe and fallow deer, as previously described for populations across Europe. In contrast, a broad PRNP variation was detected in red deer, with non-synonymous polymorphisms at codons 98, 226 and 247 as well as synonymous mutations at codons 21, 78, 136 and 185. Moreover, a novel 24 bp deletion within the octapeptide repeat was detected. In summary, 14 genotypes were seen in red deer with significant differences in their geographical distribution and frequencies, including geographical clustering of certain genotypes, suggesting "PRNP-linages" in this species. Based on data from North American CWD and the genotyping results of the European CWD cases, we would predict that large proportions of wild cervids in Europe might be susceptible to CWD once introduced to naive populations.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.